High-fat diet aggravates amyloid-beta and tau pathologies in the 3xTg-AD mouse model.
To investigate potential dietary risk factors of Alzheimer's disease (AD), triple transgenic (3xTg-AD) mice were exposed from 4 to 13 months of age to diets with a low n-3:n-6 polyunsaturated fatty acid (PUFA) ratio incorporated in either low-fat (5% w/w) or high-fat (35% w/w) formulas and compared with a control diet. The n-3:n-6 PUFA ratio was decreased independently of the dietary treatments in the frontal cortex of 3xTg-AD mice compared to non-transgenic littermates. Consumption of a high-fat diet with a low n-3:n-6 PUFA ratio increased amyloid-beta (Abeta) 40 and 42 concentrations in detergent-insoluble extracts of parieto-temporal cortex homogenates from 3xTg-AD mice. Low n-3:n-6 PUFA intake ratio increased insoluble tau regardless of total fat consumption, whereas high-fat diet incorporating a low n-3:n-6 PUFA ratio also increased soluble tau compared to controls. Moreover, the high-fat diet decreased cortical levels of the postsynaptic marker drebrin, while leaving presynaptic proteins synaptophysin, SNAP-25 and syntaxin 3 unchanged. Overall, these results suggest that high-fat consumption combined with low n-3 PUFA intake promote AD-like neuropathology.
Julien
Carl
C
Faculty of Pharmacy, Laval University, Quebec, QC, Canada.
Tremblay
Cyntia
C
Phivilay
Alix
A
Berthiaume
Line
L
Emond
Vincent
V
Julien
Pierre
P
Calon
Frédéric
F
D000544:Alzheimer Disease / Q000139:chemically induced / Q000378:metabolism*; D016229:Amyloid beta-Peptides / Q000378:metabolism*; D000818:Animals; D001921:Brain / Q000187:drug effects / Q000378:metabolism*; D004041:Dietary Fats / Q000009:adverse effects / Q000378:metabolism / Q000494:pharmacology*; D004195:Disease Models, Animal; D015525:Fatty Acids, Omega-3 / Q000009:adverse effects / Q000494:pharmacology*; D006801:Humans; D051379:Mice; D008822:Mice, Transgenic; D016875:tau Proteins / Q000378:metabolism*
D016229:Amyloid beta-Peptides; D004041:Dietary Fats; D015525:Fatty Acids, Omega-3; D016875:tau Proteins